1. Field of the Invention
The present invention generally relates to a separator for separating a solute from a solution. More particularly, the invention relates to a separator adapted for an ultrafiltration of a solute.
2. Description of Relevant Art
There has been already known an ultrafiltration process using a centrifugal separator or a filterpress or suction filter to separate a solute from a solution as a sample.
The ultrafiltration is a filtration of separating from a solution such particles as of sizes smaller than those of a normal filtration in which the size of particles to be filtered out ranges from 10.sup.5 to 10.sup.7 angstroms, that is, such a solute that has particle sizes ranging from a few dozen angstroms to a few micrometers, thus there being no particular limitations to the kind of the solution.
In this respect, due to the fact that viruses, polysaccharides, proteins, colloids, and microbes fall in such a size range, in recent years there has been found an extensive use of ultrafiltration in the field of biochemistry.
Among those ultrafiltration processes employed in the biochemical field, there is an example particularly using a centrifugal separator.
In such an ultrafiltration process, exemplarily, a blood serum or a blood plasma is selected as a test solution to separate or filter out a protein therefrom by way of an ultrafiltration. In this case, by having dissolved a low molecular substance such as an inorganic ion, a medicinal substance, or a hormone in the blood serum or the blood plasma before the ultrafiltration, there can be measured a binding fraction of such a substance with the protein, since low molecular substances bound to the protein are forced to be filtered out in the ultrafiltration.
Moreover, taking advantage of such fact, the ultra-filtration is used for separating through a membrane a low molecular substance of protein bonding type from that of protein non-bonding (free) type in a blood serum or a blood plasma.
In such way, the ultrafiltration is applied to an analysis of a low molecular substance such as an amino acid, a catechol amine, a vitamine, or a guanidine in a blood serum, in which generally a protein is needed to be removed from the blood serum.
Further, with respect to those medicinal subtances to be carried in the blood, the substanes falling into a protein (albumin) bonding type and a free type efficacious to the decease, the ultrafiltration is used also for measuring the concentration in blood of such protein free type medicinal substances.
Furthermore, as will be understood from the foregoing description, the ultrafiltration is used for an enrichment or concentration of a protein in the blood, as well. In the protein enrichment, a deionized water may be employed as solvent (buffer solution) to desalt the protein.
Incidentally, as of a disposable type adapted to put a test solution of approximately 2 ml or less to be filtered by use of a centrifuge, there is generally used such a separator as shown in FIG. 3A.
Referring now to FIG. 3A, which is a longitudinal sectional view of a separator of such type, designated at reference numeral 101 is the entirety of the separator. The separator 101 includes a test solution reservoir 103 of a cylindrical configuration open at both upper and lower ends thereof, the reservoir 103 having inside of the longtudinally intermediate part thereof a radially inwardly flanged portion 106 formed along the inner circumference thereof, a cylindrical membrane support base 104 fitted in the lower half of the solution reservoir 103, an ultrafiltration-oriented filtering membrane 105 interposed between the top face of the support base 104 and the underside of the flanged portion 106 of the solution reservoir 103 so as to extend perpendicularly to the axis of the reservoir 103, and a filtrate cup 102 detachably fitted on the lower part of the support base 104. When attaching to the centrifuge, the separator 101 has a reservoir cap (not shown) put on the solution reservoir 103. A proper part of the separator 101 is constituted with the solution reservoir 103, the filtering membrane 105, and the support base 104.
The flanged portion 106 has defined by the inner circumference thereof a circular central opening 106c for passing the test solution, while the opening 106c is wholly covered from below with the filtering membrane 105. The flanged portion 106 further has formed thereunder, along the inner circumference thereof, a radially inner ring-like projection 106a for holding from above the filtering membrane 105 and, outside of the projection 106a, a radially outer ring-like projection 106b for a welding use.
The support base 104 has a smaller diameter than the solution reservoir 103 and, when fitted therein, holds in position the filtering membrane 105 to be tight fitted between the inner projection 106a of the flanged portion 106 and a disc-like support portion 107 as the top of the support base 104. In the support portion 107, over an area thereof opposite to the opening 106c of the flanged portion 106, there are formed therethrough a plurality of small holes 107a for passing the filtrate.
In FIG. 3A, designated at reference character 103a is a solution chamber of the reservoir 103, and 104a is an outwardly flanged portion of the support base 104, which portion 104a is adapted for the attachment of the filtrate cup 102.
In the foregoing arrangement, the ultrafiltration-oriented filtering membrane 105 is made of a polysulphone, a polyvinyl chloride, a regenerated cellulose, a cellulose acetate, an acrylonitrile and vinyl chloride copolymer, or the like, and adapted for a nominal cutoff molecular weight within a range of five thousand to one million. For a filtering membrane, the term "cutoff molecular weight" means a cutoff value as specified in terms of molecular weight for molecules to be filtered through the membrane, and indirectly represents the size of surfacial pores of the membrane. For example, a filtering membrane of a cutoff molecular weight of 10,000 is adapted for the filtration of no more than those molecules not exceeding 10,000 in the molecular weight. The determination of cutoff molecular weight is made by use of a spherical protein of a known molecular weight.
The solution reservoir 103 as well as the support base 104 is made of a thermoplastic material such as an acrylic resin, a polystyrene, a polyethylene, a polypropylene, or a polycarbonate.
The outer ring-like projection 106b of the reservoir 103 and the support portion 107 of the base 104, both being made of such thermoplastic material, are joined with each other by way of an ultrasonic welding, whereas the joining therebetween may be otherwise effected. For example, though being not described herein, there is a well-known system by way of a high-frequency welding, besides one which, when assembling a separator, does not need welding but employs a clip to join a support base to a solution reservoir.
In the manufacture of the aforementioned separator 101, particularly when constituting the proper part thereof, there is employed an ultrasonic welding process which first includes steps of placing the filtering membrane 105 on the support portion 107 of the support base 104, and inserting the support base 104 from below into the lower half of the solution reservoir 103, thereby pinching to hold the membrane 105 between the support portion 107 of the base 104 and the inner ring-like projection 106a of the reservoir 103, so that the top face of the support portion 107 is brought into abutment with the lower edge of the outer ring-like projection 106b of the reservoir 103.
Next, as principal steps of the ultrasonic welding process, an unshown ultrasonic welder has an ultrasonic horn thereof forced to abut with a load on the top of the solution reservoir 103, and ultrasonic vibrations of a predetermined amplitude and a predetermined frequency are applied from the horn to the reservoir 103, thereby generating heat over the contact area between the top face of the support portion 107 and the lower edge of the outer projection 106b, welding the support portion 107 and the outer projection 106b to each other, whereby a ring-like welded portion 108 is formed. The time period for applying ultrasonic vibrations is usually within a range of 0.5 to 2 seconds, though variable with the type of employed thermoplastic material.
Recent years have found an extensive use of such an ultrasonic welding process as described above, by virtue of advantages thereof such that the generation of heat is controlled at no more than a loaded contact area as a portion to be welded, and that the weldment is completed within a very short period of time. For example, in the field of a cassette tape also, an ultrasonic welding has found a recent application thereof to the joining between upper and lower halves of a tape casing.
As will be easily understood, the separator 101 shown in FIG. 3A, which is prefabricated into a unit, is free from some shortcomings that otherwise may be encountered such as when making an ultrafiltration using a weld-less type separator of which proper body is fabricated, not by welding a support base to a solution reservoir, but by manually assembling together such two parts and a filtering membrane, with the possiblity of assembling same in error or causing a rupture of the membrane.
However, still in the separator 101, in which the welded portion 108 is positioned in close vicinity to the filtering membrane 105, the filtering membrane 105 may have a part thereof thermally melted during the ultrasonic welding process or likely to be otherwise damaged by heat.
Incidentally, with respect to the centrifuge, there are two well-known types: an angle type and a swing type, each respectively utilized in both ultrafiltration and normal filtration. In general, when put in an angle type centrifuge, separators are centrifuged into inclined positions thereof. In a swing type centrifuge, they are normally swingably suspended so as to be centifuged into substantially horizontal positions thereof.
In this respect, when the separator 101 (as applied to the ultrafiltration of a blood serum or a blood plasma) is centrifuged by an angle type centrifuge, the test solution put in the solution chamber 103a has concentration-polarized protein particles thereof dislocated under centrifugal forces to one side in the lower part of the solution chamber 103a, so that the degree of concentration polarization becomes decreased on the filtering membrane 105, thus raising the filtering rate. To the contrary, in the case of a swing type centrifuge, concentration-polarized protein particles are centrifuged to be distributed over the membrane 105, thus keeping the filtering rate lower than expected. For such reasons, the conventional separator 101 is restricted in the type selection of centrifuge.
For referential purpose, FIG. 3B is attached hereto to illustrate a state of the separator 101 as centrifuged by an unshown centrifuge of an angle type with a rotor of an approximately 45.degree. inclination. Designated at reference character P is a group of concentration-polarized protein particles, F is a test solution containing a low-molecular substance of free type, and V is a centrifugal force in the form of a vector.
The present invention has been achieved to effectively solve such problems of a conventional separator, including a thermal influence on a filtering membrane in an ultrasonic welding process in the fabrication of a proper part of the separator as well as a restriction in the type selection of centrifuge.